Immunosenescence: Mechanisms, Clinical Impacts, and Therapeutic Strategies

Extract

The term “immunosenescence” is used to describe the progressive alteration and gradual deterioration of the immune system that develop with aging. It is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly persons. Immunosenescence consists of 10 chapters summarizing the most up-to-date information with respect to the cellular and molecular mechanisms of the aging immune system. The book covers the basic biology of cell-mediated immunity decline, the consequences of the declined immune system, and interventional therapeutic approaches aiming to correct or reverse the aged immune system.

The first 4 chapters are replete with detailed information on specific age-related cellular responses involved in various components of the immune system. Chapter 1 describes our current understanding on age-associated T-cell immune decline. This chapter highlights numerous factors that can contribute to this decline, including narrowing of the T-cell repertoire, accumulation of large dysfunctional oligoclonal expansion, loss of costimulatory receptors, and increase in inhibitory receptors. The chapter specifically emphasizes the critical role of regulatory T cells in reduced immune function in aging, suggesting that an increase in numbers of regulatory T cells with age may contribute to diminished immune responses such as tumor immunity and the immune responses to foreign antigens. Chapter 2 discusses the major age-related alterations in innate immune cells such as granulocytes, macrophages, dendritic cells, and natural killer cells. This chapter gives the readers a good understanding of a chronic inflammatory state known as “inflamm-aging” as a result of accumulation of a lifetime exposure to environmental factors that trigger the production of proinflammatory molecules. Chapter 3 of the book focuses on the contribution of the thymus involution to the aging of the immune system. This chapter contains detailed information for entry-level scientists to understand the role of the thymus for immunity. The authors also provide 2 well-described examples in which unphysiological situations develop as a result of low thymus function to support the considerable contribution of thymus to immunosenescence. The chapter ends with the discussions on potential rejuvenation strategies to reactivate thymus function. Chapter 4 switches topic to age-related changes in B-cell responses. Reading this chapter, one learns that aging is associated with impaired new B-cell generation and responsiveness to antigens, smaller and fewer germinal center formations within an immune response, insufficient plasma cell numbers, and limited recall responses.